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Related Concept Videos

Prodrugs01:30

Prodrugs

Prodrugs are a class of pharmaceutical compounds that undergo a biotransformation process within the body to be converted into a pharmacologically active drug. Prodrugs are designed to improve the therapeutic properties of the parent drug, such as enhancing bioavailability, increasing stability, or reducing toxicity. The concept of prodrugs revolves around modifying the chemical structure of the original drug to make it more effective or convenient for administration.
Prodrugs help overcome...
Drug-Receptor Bonds01:25

Drug-Receptor Bonds

Drug-receptor bonds are formed through various chemical forces when drugs interact with target cells. Covalent bonds, strong and irreversible, are exemplified by DNA-alkylating anticancer agents that inhibit cell division. However, such irreversible drug binding lacks selectivity and can modify the DNA of the surrounding healthy cells. Covalent binding often contributes to tissue toxicity, as seen with chloroform and paracetamol metabolites binding to the liver, causing hepatotoxicity.
In...
Drug Metabolism: Phase II Reactions01:14

Drug Metabolism: Phase II Reactions

Phase II reactions are essential for the detoxification and elimination of drugs from the body. These reactions involve the conjugation of parent drugs or their phase I metabolites with endogenous molecules, resulting in more hydrophilic drug conjugates. The primary conjugation reactions in this phase are sulfation and glucuronidation. Both sulfation and glucuronidation typically produce biologically inactive metabolites. However, in some cases involving prodrugs, active metabolites may be...
Phase II Reactions: Sulfation and Conjugation with α-Amino Acids01:19

Phase II Reactions: Sulfation and Conjugation with α-Amino Acids

Sulfation and α-amino acid conjugation are two critical biotransformation reactions in drug metabolism. Sulfation, a phase II biotransformation reaction, involves adding a polar sulfate group to a drug, enhancing its water solubility and promoting excretion. This process can either co-occur with or occur independently of glucuronidation. Nonmicrosomal sulfotransferase enzymes catalyze the process. The reaction involves 3'-phosphoadenosine-5'-phosphosulfate or PAPS coenzyme activation, sulfur...
Drug Biotransformation: Overview01:16

Drug Biotransformation: Overview

Pharmaceutical substances known as xenobiotics are predominantly lipophilic and nonionized. This enables them to permeate lipid bilayers, such as cell membranes, and interact with intracellular target receptors. Lipophilic drugs have an advantage in crossing biological barriers and reaching their intended sites of action. However, lipophilic drugs often have a restricted capacity for renal expulsion or elimination from the body. When these drugs enter the kidneys and undergo glomerular...
Drug Biotransformation: Overview01:28

Drug Biotransformation: Overview

Biotransformation, also known as drug metabolism, is a vital physiological process that chemically alters drugs, facilitating their elimination from the body and terminating their action. This process involves two main phases: phase I and phase II reactions. Phase I reactions, including oxidation, reduction, and hydrolysis, introduce or unmask polar functional groups on the drug molecule, thereby increasing its water solubility. By enhancing water solubility, the drug becomes more hydrophilic...

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Preparation and Characterization of Lipophilic Doxorubicin Pro-drug Micelles
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Preparation and Characterization of Lipophilic Doxorubicin Pro-drug Micelles

Published on: August 2, 2016

Ester bonds in prodrugs.

Luke D Lavis1

  • 1Janelia Farm Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia 20147, USA. lavisl@janelia.hhmi.org

ACS Chemical Biology
|April 22, 2008
PubMed
Summary
This summary is machine-generated.

Prodrug ester bonds may not always break down quickly in cells. New research shows specific sugar compounds resist breakdown, indicating ester bonds can remain intact within a cellular environment.

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Area of Science:

  • Biochemistry
  • Medicinal Chemistry
  • Pharmacology

Background:

  • Prodrugs are often designed with ester bonds for improved drug delivery.
  • It is widely assumed that cellular esterases rapidly cleave these bonds, releasing the active drug.

Purpose of the Study:

  • To investigate the stability of ester bonds in prodrugs within a cellular context.
  • To determine if cellular esterases universally and completely cleave all prodrug ester bonds.

Main Methods:

  • Structure-activity relationship studies were conducted.
  • Regioisomeric acylated sugar compounds were synthesized and analyzed.
  • Biological activity of different regioisomers was compared.

Main Results:

  • Disparate biological activity was observed among regioisomeric compounds.
  • This suggests that specific ester bonds can resist cleavage by endogenous esterases.
  • Ester bonds in certain prodrug structures may persist in the cellular environment.

Conclusions:

  • The assumption of rapid and complete ester bond cleavage in prodrugs is challenged.
  • Cellular esterase activity can be specific, allowing ester bonds to remain intact.
  • Prodrug design strategies may need to account for variable ester bond stability.